Project description:Prior studies support the notion that the experimental chemopreventive agent, genistein, inhibits prostate cancer (PCa) cell movement in humans and that this in turn inhibits metastatic spread, thereby preventing PCa-specific death. As many effects have been ascribed to genistein, it has been considered a non-specific agent. However, its effects are concentration-dependent, and the vast majority of studies use concentrations greater than 3 logs above those associated with dietary consumption. Genistein is found in soy, and individuals consuming soy-based diets have blood concentrations of free genistein in the low nanomalar range. Using dosing guided by phase I pharmacokinetic studies in US men, prospective treatment of men on a phase II trial with genistein for one month prior to radical prostatectomy for localized PCa. Here we conducted an unbiased screening for effects of genistein in prostate as well as evaluate changes between normal and cancer cells.
Project description:To identify molecular effects of genistein on mRNA levels in prostate cancer, we compared gene expression profiles of genistein-treated tumors with placebo-treated samples. There were 628 probes that reached nominally significant p-values. The genes that were differentially expressed between genistein and placebo samples were involved in angiogenesis, apoptosis, epithelial to mesenchymal transition, and tumor progression. Gene enrichment analysis suggested that PTEN and PDGF were activated, while MYC, beta-estradiol, glucocorticoid receptor NR3C1, and interferon-gamma were repressed in response to genistein treatment. These findings highlight the effects of genistein on global changes in gene expression in prostate cancer and its effects on molecular pathways involved in prostate tumorigenesis.
Project description:We have investigated the effects of genistein on several prostate cancer cell lines, including the ARCaP-E/ARCaP-M model of the epithelial-to-mesenchymal transition (EMT), to analyze effects on their epigenetic state. In addition, we investigated the effects of combined treatment of genistein with the histone deacetylase inhibitor vorinostat on survival in prostate cancer cells. Using whole-genome expression profiling and whole-genome methylation profiling, we have determined the genome-wide differences in genetic and epigenetic responses to genistein in prostate cancer cells before and after undergoing the EMT. Also, cells were treated with genistein, vorinostat, and a combination treatment, where cell death and cell proliferation was determined.
Project description:We have investigated the effects of genistein on several prostate cancer cell lines, including the ARCaP-E/ARCaP-M model of the epithelial-to-mesenchymal transition (EMT), to analyze effects on their epigenetic state. In addition, we investigated the effects of combined treatment of genistein with the histone deacetylase inhibitor vorinostat on survival in prostate cancer cells. Using whole-genome expression profiling and whole-genome methylation profiling, we have determined the genome-wide differences in genetic and epigenetic responses to genistein in prostate cancer cells before and after undergoing the EMT. Also, cells were treated with genistein, vorinostat, and a combination treatment, where cell death and cell proliferation was determined.
Project description:We have investigated the effects of genistein on several prostate cancer cell lines, including the ARCaP-E/ARCaP-M model of the epithelial-to-mesenchymal transition (EMT), to analyze effects on their epigenetic state. In addition, we investigated the effects of combined treatment of genistein with the histone deacetylase inhibitor vorinostat on survival in prostate cancer cells. Using whole-genome expression profiling and whole-genome methylation profiling, we have determined the genome-wide differences in genetic and epigenetic responses to genistein in prostate cancer cells before and after undergoing the EMT. Also, cells were treated with genistein, vorinostat, and a combination treatment, where cell death and cell proliferation was determined. ARCAP-E, ARCAP-M, and normal human PrEC cells were analyzed for genome-wide methylation using the Illumina 27K CpG Methylation BeadChip. ARCAP-E and ARCAP-M cells were treated with DMSO as a negative control, genistein, or 5-aza-deoxycytidine as a positive control for demethylation. PrEC cells, used as a normal human prostate cell line control, were untreated.
Project description:We have investigated the effects of genistein on several prostate cancer cell lines, including the ARCaP-E/ARCaP-M model of the epithelial-to-mesenchymal transition (EMT), to analyze effects on their epigenetic state. In addition, we investigated the effects of combined treatment of genistein with the histone deacetylase inhibitor vorinostat on survival in prostate cancer cells. Using whole-genome expression profiling and whole-genome methylation profiling, we have determined the genome-wide differences in genetic and epigenetic responses to genistein in prostate cancer cells before and after undergoing the EMT. Also, cells were treated with genistein, vorinostat, and a combination treatment, where cell death and cell proliferation was determined. ARCaP-E and ARCaP-M cells were analyzed for whole genome expression using the Illumina HumanHT-12 Expression BeadChip. Samples were treated with DMSO control, genistein, vorinostat, a combination of vorinostat and genistein, or 5-aza-deoxycytidine. Samples were prepared in triplicate on independent days.
Project description:To identify molecular effects of genistein on DNA methylation in prostate cancer, we compared DNA methylation profiles of genistein-treated tumors with placebo-treated samples. There were 156 probes with significantly increased methylation in placebo-treated cases versus normal tissues that were not significant between genistein-treated cases and normal tissues, suggesting that genistein may have had some demethylation effects. These 156 probes corresponded to at least 92 separate genes including ADCY4, ALOX12, HAAO, LRRC4, NEU1, RAPGEFL1, and WNT7B.These findings highlight the effects of genistein on global changes in DNA methylation in prostate cancer and its effects on molecular pathways involved in prostate tumorigenesis.
Project description:Gene expression profiling to identify genes significantly modulated by low and high doses of genistein in LNCaP cells. Significant genes were identified using StepMiner analysis and significantly altered pathways with Ingenuity Pathways analysis. Genistein significantly altered expression of transcripts involved in cell growth, carcinogen defenses and steroid signaling pathways. The effects of genistein on these pathways were confirmed by directly assessing dose-related effects on LNCaP cell growth, NQO-1 enzymatic activity and PSA protein expression. A compound treatment design type is where the response to administration of a compound or chemical (including biological compounds such as hormones) is assayed.
Project description:Gene expression profiling to identify genes significantly modulated by low and high doses of genistein in LNCaP cells. Significant genes were identified using StepMiner analysis and significantly altered pathways with Ingenuity Pathways analysis. Genistein significantly altered expression of transcripts involved in cell growth, carcinogen defenses and steroid signaling pathways. The effects of genistein on these pathways were confirmed by directly assessing dose-related effects on LNCaP cell growth, NQO-1 enzymatic activity and PSA protein expression.
Project description:Genistein is one of the flabonoids which is included in high concentration in soy and has a high estrogenic activity. Beneficial effects of estrogen or hormone replacement therapy (HRT) on muscle mass or muscle atrophy have been demonstrated. We investigated the preventive effects and underlying mechanisms of genistein intake on denervation-induced muscle atrophy. Genistein intake significantly suppressed the loss of soleus muscle weight and the denervation-induced up-regulations of FOXO1 protein. The results of a DNA microarray showed that the estrogen receptor (ER) target genes are changed by genistein intake. Genistein suppressed the soleus muscle atrophy, and it was attenuated under the ER antagonist treatment. The administration of an ERα agonist suppressed the denervation-induced muscle atrophy and up-regulation of Atrogin1 gene expression, but the ERβ agonist had no effect.